tbuckley/cabot-search huggingface dataset:
P427: THE SINGLE CELL T CELL LANDSCAPE OF AML PATIENTS POST ALLOGENEIC STEM CELL TRANSPLANTATION
Authors: A. Mathioudaki, X. Wang, R. Huth, J. Zaugg, C. Pabst
Journal: HemaSphere (2022)

Background: In Acute myeloid leukemia (AML), chemotherapy may lead to long-term remission, but allogeneic stem cell transplantation (alloSCT) often remains the only curative therapeutic approach, particularly in AML with high-risk genetics. However, not every patient responds to alloSCT. Several hypotheses have been associated with therapy failure, such as the incapability of T cells to recognize and eliminate residual leukemia stem cells (LSCs), which thus escape the graft-versus-leukemia (GVL) effect. However, the role of the T cells’ repertoire in therapy outcome still remains unclear. Aims: Here, we investigated the impact of the bone marrow (BM) T cell composition on the therapy outcome of AML patients after alloSCT. Methods: We performed single-cell RNA sequencing (scRNA-seq) of T cells and hematopoietic stem and progenitor cells (HSPCs) isolated from BM aspirates 100 days post alloSCT of three patients in complete remission (CR) versus three suffering relapse (REL). We investigated the prognostic impact of putative T-cell biomarkers in therapy outcome, using flow cytometry analysis on an independent cohort. Results: Using scRNA-seq, we identified 21 T cell and 9 HSPC populations and observed differences in T cell population abundances between REL and CR. In particular, we observed an enrichment of specific CD8+ T cell subsets in the CR group, while certain CD4+ T cell subsets, such as regulatory T cells were enriched in REL patients. Furthermore, we observed an increased T cell cytotoxicity signature in the CR group, that potentially contributes to better clinical outcome. Within the genes upregulated in the CR condition, we identified surface molecules linked to T cell cytotoxicity. Subsequent flow cytometry analysis corroborated a link between these markers and better clinical outcome. Our data suggest that the early bone marrow T cell signature post alloSCT might reflect GVL-effects required to achieve long-term survival. Image:Summary/Conclusion: Understanding the role of T cell composition on therapy response may offer novel approaches for both predicting prognosis as well as developing new therapeutic strategies.
P516: ADULT LANGERHANS CELL HISTIOCYTOSIS WITH THYROID GLAND INVOLVEMENT: CLINICAL PRESENTATION, GENOMIC ANALYSIS AND OUTCOME
Authors: H. Cai, T. Liu, H. Cai, M. Duan, J. Li, D. Zhou, X. Cao
Journal: HemaSphere (2022)

Background: Langerhans cell histiocytosis (LCH) is a rare, clonal disorder derived from CD1a-positive and CD207-positive immature myeloid dendritic cells. The clinical presentations and outcomes of LCH are extremely variable. Thyroid gland involvement is rare, and solitary thyroid gland involvement with LCH is extremely rare, with most cases presenting as part of multisystem disease.Until now, little information exists on the genomic analysis of LCH with thyroid gland involvement with or without coexisting papillary thyroid carcinoma. Aims: To evaluate the characteristics and treatment outcomes of adult Langerhans cell histiocytosis (LCH) patients with thyroid involvement. Methods: We retrospectively described the clinical, biological, and genomic characteristics of a series of 36 LCH patients with thyroid involvement in our centre between January 2001 and December 2021. Results: We retrospectively described the clinical, biological, and genomic characteristics of a series of 36 LCH patients with thyroid involvement in our centre between January 2001 and December 2021. At the time of diagnosis, only 1 patient was classified as having single-system LCH, and 35 patients were classified as having multisystem (MS) LCH. Three patients had coexisting papillary thyroid carcinoma. Patients with thyroid gland involvement had higher frequencies of pituitary (88.6% vs. 53.4%, P<0.001), liver (45.7% vs. 20.7%, P=0.003) and lymph node (54.3% vs. 31.6%, P=0.012) involvement and a lower frequency of bone (45.7% vs. 72.0%, P=0.003) involvement than patients without thyroid gland involvement. Sixteen patients had abnormal thyroid function, including 9 patients with primary hypothyroidism, 1 patient with central hypothyroidism, and 6 patients with subclinical hypothyroidism. BRAFV600E, BRAFN486_P490 and MAP2K1 mutations were detected in 14.3%, 57.1% and 7.1% of patients, respectively. After a 43-month median follow-up, none of the patients died, and 15 patients experienced reactivation. The median event free survival was 37.5 months. Two of 6 patients with subclinical hypothyroidism had normal thyroid function, and 12 patients still had hypothyroidism after treatment. Summary/Conclusion: As the largest adult LCH cohort with thyroid gland involvement to date, we found that patients with thyroid gland involvement had different clinical characteristics, genetic profiles and outcomes than patients without thyroid gland involvement.
S239: COMPARABLE LONG-TERM OUTCOMES BETWEEN UPFRONT HAPLOIDENTICAL AND IDENTICAL SIBLING DONOR HSCT IN APLASTIC ANEMIA: A NATIONAL REGISTRY-BASED STUDY
Authors: Z. xu, L. xu, D. wu, S. wang, X. zhang, R. xi, S. gao, L. xia, J. yang, M. jiang, X. wang, Q. liu, J. chen, M. zhou, X. huang
Journal: HemaSphere (2022)

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for severe aplastic anemia (SAA), and transplantation from identical sibling donors (ISDs) has been recommended as a first-line treatment. Aims: Haploidentical donor (HID) transplantation for SAA has made great advances; thus, an increased role of HID-SCT in SAA should be considered if an ISD is unavailable. Methods: We performed a national registry-based analysis comparing long-term outcomes in the upfront HID or upfront ISD SCT setting. Results: A total of 342 SAA patients were enrolled, with 183 patients receiving HID SCT and 159 receiving ISD SCT. The estimated 9-year overall survival (OS) and failure-free survival (FFS) were 87.1±2.5% and 89.3±3.7% (P = 0.173) and 86.5±2.6% vs. 88.1±3.8% (P = 0.257) for patients in the HID and ISD SCT groups, respectively. Transplantation from HID or ISD SCT has greatly improved quality of life (QoL) levels post-HSCT compared to pre-HSCT. The occurrence of chronic graft versus host disease was the only identified adverse factor affecting each subscale of QoL. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were all similar between HID and ISD SCT at 5-year points. At the last follow-up, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. A total of 342 SAA patients were enrolled, with 183 patients receiving HID SCT and 159 receiving ISD SCT. The estimated 9-year overall survival (OS) and failure-free survival (FFS) were 87.1±2.5% and 89.3±3.7% (P = 0.173) and 86.5±2.6% vs. 88.1±3.8% (P = 0.257) for patients in the HID and ISD SCT groups, respectively. Transplantation from HID or ISD SCT has greatly improved quality of life (QoL) levels post-HSCT compared to pre-HSCT. The occurrence of chronic graft versus host disease was the only identified adverse factor affecting each subscale of QoL. Physical and mental component summaries in adults as well as physical, mental, social, and role well-being in children were all similar between HID and ISD SCT at 5-year points. At the last follow-up, the proportion of returning to society was comparable between the HID and ISD groups, showing 78.0% versus 84.6% among children and 74.6% versus 81.2% among adults. Image:Summary/Conclusion: These data suggest the recommendation for upfront transplantation with a haploidentical donor for SAA patients in the absence of an ISD, especially in experienced transplant centers.
P1192: ASIA SUBPOPULATION ANALYSIS FROM THE PHASE III POLARIX TRIAL
Authors: Y. Song, J. Jin, H. Tilly, H. Zhang, J. Cao, J. Feng, L. Zhang, S. Rai, H. Goto, Y. Terui, W. S. Kim, H.-J. Shin, J.-P. Gau, C.-H. Tsai, J. P. Sharman, L. Bu, J. Hirata, C. Lee, K. Izutsu, J. Zhu
Journal: HemaSphere (2022)

Background: In the pivotal Phase III POLARIX trial (NCT03274492), Pola-R-CHP demonstrated significantly improved progression-free survival (PFS) compared with R-CHOP, with a similar safety profile in patients with previously untreated diffuse large B-cell lymphoma (DLBCL; Tilly et al. 2022). An Asia subpopulation analysis was included as part of the trial design. Aims: To analyze patients enrolled in Asia for the purpose of registration of the POLARIX trial in China. Methods: Patients from mainland China, Hong Kong, Japan, South Korea, and Taiwan (enrolled during the global phase), and from the China extension cohort were included in the Asia subpopulation. All patients provided informed consent. POLARIX methods were previously described (Tilly et al. 2022). Briefly, patients with untreated DLBCL were randomized 1:1 using the same stratification factors to receive six cycles of Pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. Pola-R-CHP is an investigational combination. The purpose of this analysis was to evaluate consistency of PFS (defined as ≥50% risk reduction in PFS) in the Asia subpopulation with the global population. Results: Overall, 281 patients (intent-to-treat population; 150, 85, 31 and 15 patients in mainland China, Japan, South Korea and Taiwan, respectively) were analyzed (141 received Pola-R-CHP and 140 received R-CHOP); 160 patients from the global population and 121 from the China extension cohort. Median age was 63 (range 19–79) years, and most patients had an International Prognostic Index of 3–5 (61.9%). At the data cut-off of June 28, 2021 (median follow-up of 24.2 months), PFS was superior with Pola-R-CHP vs R-CHOP (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.40–1.03) and met the consistency definition with the global population. The 2-year PFS rate was 74.2% (95% CI: 65.7–82.7) with Pola-R-CHP vs 66.5% (95% CI: 57.3–75.6) with R-CHOP. Other key efficacy results were similar to the global study results (Table 1). The safety profile was generally comparable for Pola-R-CHP vs R-CHOP, including rates of grade 3–4 adverse events (AEs; 72.9% vs 66.2%), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to discontinuation of any study treatment (7.2% vs 5.0%), and incidence of peripheral neuropathy (all grades, 44.3% vs 50.4%), respectively. Image:Summary/Conclusion: The results from the Asia subpopulation of POLARIX were consistent with the global study, with a clinically meaningful improvement in PFS (risk of disease progression, relapse or death reduced by 36%) following treatment with Pola-R-CHP vs R-CHOP, and a comparable safety profile in Asian patients with previously untreated DLBCL.
P1113: PROGNOSTIC ROLE OF GENETIC ABNORMALITIES IN MANTLE CELL LYMPHOMA
Authors: E. Kleina, S. Voloshin, J. Vokueva, O. Petukhova, L. Martynenko, M. Bakai, J. Ruzhenkova, S. Linnikov, E. Kariagina, O. Uspenskaia, I. Ziuzgin, S. Bessmelcev, S. Sidorkevich, I. Martynkevich
Journal: HemaSphere (2022)

Background: Mantle cell lymphoma (MCL) – B-cell lymphoma with a high frequency of genome instability associated with a recurrent clinical course, short non-progressive and overall survival. Special attention is paid to the “double-hit” MCL (simultaneous presence of translocations of CCND1 and C-MYC genes), characterized mainly by a pleomorphic/blastoid morphological variant, refractory clinical course and unfavorable prognosis. Aims: To identify the spectrum and frequency of occurrence of genetic anomalies and their effect on the course of MCL. Methods: The results of a standard cytogenetic study (G-banding) in 51 and FISH studies in 75 patients with MCL are presented. Results: In a standard cytogenetic study, a pathological karyotype was found in 25/51 (49,0%) patients. Translocation t(11;14)(q13;q32) was detected in 23/51 (45,1%) patients. As part of the complex karyotype, t(11;14) was determined in 16/51 (31,4%) cases. The FISH study made it possible to additionally identify genetic aberrations in patients with MCL. In patients with normal karyotype t(11;14) was found in 18/51 (35,3%) cases. C-MYC gene rearrangements were detected in 16/75 (21,3%) cases. In this group, genetic abnormalities were found in 7/11 (63,6%) patients (in 5 patients, mitoses were not obtained). In all patients t(11;14) was detected either as a single genetic aberration (in 1/7 (14,3%)) or as part of a complex karyotype (in 6/7 (85,7%)) in combination with genetic abnormalities 7 and 17 chromosomes. In 8/16 (50,0%) patients, C-MYC gene rearrangements were combined with a deletion of the TP53 gene. In 59/75 (78,7%) cases, C-MYC gene rearrangements were not detected. Chromosomal aberrations were found in 18/39 (46,2%) patients, including complex karyotype changes in 10/18 (55,6%) patients. Translocation t(11;14) - in 16/18 (88,9%) cases. TP53 gene deletion was detected in 10/59 (16,9%) patients. Data analysis showed a significant adverse effect of the complex karyotype, TP53 deletion, C-MYC rearrangement on the clinical course of MCL compared with the standard risk group. The median progression-free survival in high molecular risk patients was 12,5 months; the median progression-free survival was not achieved in the standard risk group. Summary/Conclusion: An integrated approach to the genetic diagnosis of MCL using standard cytogenetic and FISH studies makes it possible to identify a high-risk group: “double-hit” and with complex changes in the karyotype. It was also shown that in the group of patients with changes in the C-MYC gene, additional genetic anomalies were more often detected, which are an unfavorable prognostic factor: a complex karyotype (the presence of three or more aberrations) – 37,5% and 16,9%, and aberrations involving the gene TP53 – 50,0% and 16,9%. Changes in these genes are associated with shorter progression-free survival rates.
P759: CORRELATION ANALYSIS OF DNA METHYLATION LEVEL AND CLINICAL CHARACTERISTICS IN JMML PATIENTS
Authors: Y. Cai, J. Zhang, M. Yi, X. Liu, X. Zhang, Y. Wan, L. Chang, L. Zhang, X. Chen, Y. Guo, Y. Zou, Y. Chen, Y. Zhang, W. Yang, X. Zhu
Journal: HemaSphere (2022)

Background: As a rare, aggressive pediatric myeloproliferative disease, juvenile myelomonocytic leukemia (JMML) encompassed both biological features of myelodysplastic syndrome and myeloproliferative neoplasm. Studies have shown that the methylation level in JMML patients is closely related to prognosis, and patients with high methylation level have poor prognosis. Aims: This study aimed to find clinical indicators that were associated with different methylation levels and prognosis. Methods: The clinical information of 24 JMML patients with DNA samples admitted to our center from December 2013 to May 2020 was retrospectively analyzed, and the DNA methylation level of their whole genome was detected. Results: The median age of onset was 14.5 months (0.1-153 months) among the 24 cases, including 17 males and 7 females. At diagnosis, the median WBC count was 27.1×109/L (6.2-98.1×109/L), and the median platelet count was 38×109/L (10-277×109/L). Chromosome karyotype abnormalities were found in 12.5% (3/24) of patients. Next-generation sequencing results showed that 79.2% (19/24) patients had at least one Ras pathway-related classical gene mutation, and 41.7% (10/24) patients had two or more somatic mutations. Genomic DNA methylation levels were divided into three groups: 11 cases in the hypomethylation group, 2 cases in the moderate methylation group, and 11 cases in the hypermethylation group. The concordance rate of our methylation subgroup compared with the international consensus classification was 91.7%. There were significant differences in age, platelets, PTPN11 gene mutation and the number of somatic mutations ≥2 in different methylation groups (P<0.05). Correlation analysis showed that hypermethylation level was significantly correlated with PTPN11 gene mutation and ≥2 somatic mutations (P<0.001). Image:Summary/Conclusion: JMML patients with high methylation level in the DNA genome at diagnosis were older and with lower platelet levels, and hypermethylation were significantly correlated with high-risk prognostic factors such as PTPN11 gene mutation and ≥2 somatic mutations.
Textile‐Integrated Liquid Metal Electrodes for Electrophysiological Monitoring
Authors: Braden M. Li, Brandon L. Reese, Katherine Ingram, Mary E. Huddleston, Meghan Jenkins, Allison Zaets, Matthew Reuter, Matthew W. Grogg, M. Tyler Nelson, Ying Zhou, Beomjun Ju, Busra Sennik, Zachary J. Farrell, Jesse S. Jur, Christopher E. Tabor
Journal: Advanced Healthcare Materials (2022)

Abstract Next generation textile‐based wearable sensing systems will require flexibility and strength to maintain capabilities over a wide range of deformations. However, current material sets used for textile‐based skin contacting electrodes lack these key properties, which hinder applications such as electrophysiological sensing. In this work, a facile spray coating approach to integrate liquid metal nanoparticle systems into textile form factors for conformal, flexible, and robust electrodes is presented. The liquid metal system employs functionalized liquid metal nanoparticles that provide a simple “peel‐off to activate” means of imparting conductivity. The spray coating approach combined with the functionalized liquid metal system enables the creation of long‐term reusable textile‐integrated liquid metal electrodes (TILEs). Although the TILEs are dry electrodes by nature, they show equal skin‐electrode impedances and sensing capabilities with improved wearability compared to commercial wet electrodes. Biocompatibility of TILEs in an in vivo skin environment is demonstrated, while providing improved sensing performance compared to previously reported textile‐based dry electrodes. The “spray on dry—behave like wet” characteristics of TILEs opens opportunities for textile‐based wearable health monitoring, haptics, and augmented/virtual reality applications that require the use of flexible and conformable dry electrodes.
P1470: NATURAL HISTORY AND RATE OF PROGRESSION OF RETINOPATHY IN PATIENTS WITH SICKLE CELL DISEASE: AN 11-YEAR RETROSPECTIVE FOLLOW-UP ANALYSIS
Authors: R. Brandsen, R. Diederen, S. Bakhlakh, E. Nur, R. Schlingemann, B. Biemond
Journal: HemaSphere (2022)

Background: Sickle cell disease (SCD) is characterized by chronic haemolysis and recurrent vaso-occlusion, resulting in tissue ischemia and organ damage. The retina is very sensitive to ischemic damage, which can result in sickle cell retinopathy (SCR). SCR can be divided into non-proliferative sickle cell retinopathy (NPSCR) and proliferative sickle cell retinopathy (PSCR). The proliferative form can be complicated by severe visual impairment due to vitreous haemorrhage and retinal detachment. Knowledge of risk factors for progression of SCR and subsequent complications is limited. Aims: The aim of our study is to describe the natural history of SCR in a systematically analysed cohort of patients with SCD and to identify risk factors for the development of PSCR. Methods: In our retrospective cohort study, we recruited all patients with SCD (HbSS, HbSC, HbSβ0 and HbSβ+) attending the departments of Haematology and Ophthalmology between 2006 and 2011. Patients lost to follow-up were excluded. Clinical, ophthalmologic and laboratory data were systematically collected and retrospectively analysed. Univariate and multivariate binary logistic regressions were used to identify associations between clinical and laboratory variables and progression to PSCR. Results: 129 SCD patients were included with a median follow-up of 11 years (IQR = 8.5-12). The median age at the end of follow-up was 34 years (IQR = 28-45). HbSS/HbSβ0 genotype was present in 54.3% (n = 70) of the patients and HbSC/HbSβ+ genotype was present in 45.7% (n = 59). Progression of SCR during follow-up was seen in 28.7% (n = 37) of the patients. Age (aOR: 1.060, 95% CI: 1.016-1.106, p = .007) and HbSC/HbSβ+ genotype (aOR: 17.487, 95% CI: 3.494-87.519, p <.001) were associated with PSCR at the end of follow-up. No signs of SCR at the end of follow-up was significantly associated with female sex (aOR: 3.113, 95% CI: 1.418-6.834, p = .005) and HbSS/HbSβ0 genotype (aOR: 3.516, 95% CI: 1.095-11.288, p = .035). Summary/Conclusion: Progression of SCR was seen in more than a quarter of the patients. Age and HbSC/HbSβ+ genotype were associated with progression to PSCR at end of follow-up. Female SCD patients and patients with HbSS/HbSβ0 genotype were at significant lower risk of developing SCR than other patients. Given the high rate of progression of SCR, screening of SCR remains important, but differentiated strategies for screening and follow-up of SCR could be considered for low-risk or high-risk patients.
P550: A PHASE 3, RANDOMIZED TRIAL OF MAGROLIMAB IN COMBINATION WITH VENETOCLAX AND AZACITIDINE IN PREVIOUSLY UNTREATED PATIENTS WITH ACUTE MYELOID LEUKEMIA INELIGIBLE FOR INTENSIVE CHEMOTHERAPY (ENHANCE-3)
Authors: N. G. Daver, K. Liu, S. Werneke, E. Rustia, G. Ramsingh, P. Vyas
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) is an aggressive clonal hematopoietic malignancy of myeloid cells associated with limited outcomes for patients who are ineligible for intensive chemotherapy due to age or comorbidities. Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a “don’t eat me” signal on cancer cells, resulting in tumor phagocytosis by macrophages. A triplet regimen of magrolimab + azacitidine + venetoclax has shown promising activity in patients with AML. Aims: To evaluate the efficacy, safety, and tolerability of magrolimab + azacitidine + venetoclax in previously untreated patients with AML who are ineligible for intensive chemotherapy. Methods: This is a phase 3, randomized, double-blind, placebo-controlled, multicenter study. Approximately 432 patients will be randomized 1:1 to receive magrolimab + azacitidine + venetoclax (experimental arm) or placebo + azacitidine + venetoclax (control arm) (Figure). Randomization will be stratified by age, cytogenetic risk group, and geographic region. Patients are eligible if they are ≥75 years of age or 18 to 74 years of age with specific comorbidities. Receipt of prior antileukemic therapy for AML is not allowed. Magrolimab will be administered intravenously with an initial 1 mg/kg priming dose on days 1 and 4 to mitigate on target anemia. The dose will then be escalated to 15 mg/kg on day 8, then to 30 mg/kg on days 11 and 15, then weekly for 5 doses, followed by every other week beginning 1 week after the fifth weekly 30 mg/kg dose. Placebo will be dosed at the same frequency as magrolimab. Venetoclax will be administered orally at 100 mg on day 1, 200 mg on day 2, and 400 mg daily starting on day 3 and thereafter. Azacitidine will be given intravenously or subcutaneously at 75 mg/m2 on days 1 to 7, or days 1 to 5 and 8 to 9 of 28-day cycles. Patients will remain on study until disease progression, relapse, loss of clinical benefit, or unacceptable toxicities, or until other discontinuation criteria are met. The dual primary endpoints are complete remission (CR) rate within 6 treatment cycles and overall survival. Secondary endpoints include duration of CR, transfusion independence, and event-free survival. Results: Trial in progress. Image:Summary/Conclusion: Patient enrollment is ongoing. Clinical trial information: NCT05079230.